Topical Progesterone Is a Scam
That doesn’t stop providers from prescribing it or pharmacies from making it
People love to complain about Big Pharma as a nefarious group of evildoers foisting pharmaceuticals on an unsuspecting public for profit. And while there are many issues with Big Pharma, they pale in comparison with Big Natural.
I mean, what would you call promoting and selling a poorly tested and possibly unsafe product that is not recommended by the experts in the field? Helpful? Empowerment? Advocacy? I’d call it a scam. And that is exactly what we have with topical progesterone creams and gels for menopausal hormone therapy, and sadly, there are plenty of providers willing to prescribe it and compounding pharmacies willing to fill it.
I’ve mentioned on Instagram that topical progesterone is a scam, and each time someone gets upset. Sometimes they even reply with an article that suggests otherwise, but the topical progesterone industry is based on cherry-picking from low-quality data. I don’t blame the people who have been misled, but I am very angry at those who have misled them.
Why Do You Need Progesterone?
There is only one reason that progesterone needs to be given to women with menopausal symptoms—if women are taking an estrogen and they have a uterus. This is because estrogen stimulates the lining of the uterus and progesterone counteracts this effect. If the estrogen were allowed to stimulate the lining of the uterus unopposed by progesterone, it would get thick and could break off intermittently, producing irregular bleeding. More importantly, unopposed estrogen can lead to endometrial cancer (cancer of the lining of the uterus).
As an aside, progesterone may be prescribed for other reasons in menopause. The most common is to help with sleep.
A variety of different hormones can be used to counteract the effect of estrogen, either progesterone or one of the progestins, which are progesterone-like hormones. They often get a bad rap, but progestins are typically better at opposing the effect of estrogen, so someone with persistent bleeding issues on menopausal hormone therapy may have less bleeding with a progestin over a progesterone. Together, progesterone and progestins are known as progestogens. There are advantages and disadvantages to both, but as this is a post about progesterone, we won’t get into the pros and cons here. (If you want more about the advantages and disadvantages of progesterone versus progestins, I address it in detail in The Menopause Manifesto.)
Getting Progesterone into Your Body
Getting progesterone into a formulation that could be absorbed orally was biochemically tricky and didn’t happen until the 1980s. Oral progesterone is called micronized progesterone, because the process that alters progesterone so it can be absorbed from the gut is called micronization. In addition to pharmaceutical-grade oral progesterone, there is also pharmaceutical-grade vaginal progesterone. There is no commercially available pharmaceutical-grade topical progesterone.
There Is No Commercially Available Topical Progesterone for a Reason
Hormones like estradiol (the main estrogen in menopausal hormone therapy) or progesterone can’t just be made in a lab and then swallowed or put on your skin. First, they require testing to see if they even absorb into the bloodstream for each route of delivery (by mouth, across the skin, or vaginally) and if so, do they produce the right levels in the blood? Typically, this is measured with venous blood (the blood that is taken whenever you have a standard blood test). However, it’s not enough to know that the levels in the blood are high enough; a hormone must also be tested to prove that it does what it claims. So with estrogen, that might be proof that it reduces hot flushes or that it treats vaginal dryness. With progesterone, that is the ability to oppose the effect of estrogen on the lining of the uterus. This can only be accomplished with a study that uses biopsies (tissue samples) from the lining of the uterus to check for the effect of progesterone under the microscope (progesterone produces very distinct changes that are easily identified by a pathologist, if those changes don’t exist, progesterone didn’t make it there).
There are no quality studies showing topical progesterone protects the lining of the uterus. There aren’t even quality studies that show the blood levels are even in the right range. This is an important point, so I’m going to repeat it. There is no data to say that topical progesterone can protect the lining of the uterus from the cancer-causing effect of estrogen. This is a fact.
When a medication is submitted to the FDA for approval, all kinds of data is required to show exactly how much hormone is absorbed, how quickly it is absorbed, and if there are specific effects on tissues. This data is available for anyone to see in the product monograph (package insert). I use a pharmaceutical estradiol patch, so I have accurate data about that at my fingertips. And this matters because too much or too little of a hormone could have serious medical consequences. For example, too much estrogen might increase the risk of cancer and too little wouldn’t protect against osteoporosis. And too little progesterone (or none at all) won’t protect the uterus.
This safety testing is not available for compounded medications, whether they are topical or oral for that matter, because it doesn’t exist.
It turns out making hormones is pretty complicated and the years of research and strict manufacturing standards from pharmaceutical companies actually matter. A recent report from the National Academy of Sciences details the litany of issues with compounded hormones and recommends including progesterone (along with every other hormone that may be prescribed for menopause) on the difficult-to-compound list. Difficult-to-compound products require more oversight, not less.
Isn’t the Lack of Topical Progesterone a Big Pharma Ploy?
The lack of pharmaceutical-grade topical progesterone isn’t some Big Pharma scheme. Clearly Big Pharma knows there is a desire for topical products, hence the wide array of topical estradiol preparations (I mean, there are a lot!). Big Pharma is also interested in progesterone, hence there are oral and vaginal formulations. There is no topical progesterone because Big Pharma has dabbled in topical progesterone and those studies failed to produce the desired effect, meaning they did not demonstrate the progesterone could protect the uterus or even get high enough blood levels.
If Big Pharma could figure out topical progesterone, we’d have it. And yet, the people who promote compounded topical progesterone want you to believe that compounding pharmacies have somehow cracked the topical progesterone code. I guess they are keeping those studies secret?
Show Me the Data!
You got it!
Progesterone is simply not absorbed well topically. One reason is likely because it is so lipophilic, meaning it dissolves in fat. It likely gets hung up in the lipids in the skin cells and the fatty layer in the dermis, so none makes it into the bloodstream.
Several studies have shown very low blood levels of progesterone after topical application, levels that are too low to protect the uterus (see the references below). One study showed that levels of progesterone were high in the saliva and the capillaries (small blood vessels), but not in the bloodstream, which is where it matters. One hypothesis is the levels accumulate in the saliva because it accumulates there for removal. Regardless, high levels in the saliva are not a marker for what is happening in the blood, and salivary hormone testing for menopause is a total scam and I recommend avoiding any practitioner who recommends it. That is one of my get up and walk out the door rules. Never see a provider who recommends salivary hormone testing.
Studies have also failed to show that topical progesterone helps with any symptoms of menopause, which is not surprising as it isn’t absorbed well. There is one study from 1999 that suggested topical progesterone cream could reduce hot flushes, but it has some significant flaws and given the bulk of the data likely should not be considered as quality information
What Is the Origin of the Topical Progesterone Industry?
And it is an industry, lots of people are making money prescribing it and filling those prescriptions and also from ordering the useless salivary testing for “monitoring.”
The topical progesterone industry dates to the 1970s when Dr. John Lee, a family doctor, started promoting topical progesterone. Dr. Lee never published any credible research, just some anecdotes. He had some pretty biologically implausible hypotheses about progesterone that he never proved with research (basically he had some wild ideas not supported by basic biology). Dr. Lee also appears to have been one of the grandfathers of salivary testing. His reason for testing the saliva is an equally wild and totally unproven hypothesis. It seems he believed that progesterone was transported in the membranes of red blood cells and somehow diffused into the saliva, which is why blood levels didn’t reflect the progesterone in the body, but the saliva did. This is untrue. Progesterone is transported by binding proteins, and a very small percentage is free in the blood (this is common with hormones).
Dr. Lee is also the father of the totally meaningless term “estrogen dominance” that is still used today to sell useless salivary hormone tests.
Seriously, Please Don’t Rely on Topical Progesterone for Your Health
I encourage anyone who wants to read more to check out this excellent article on the subject.
Topical progesterone is not any more or less natural than oral progesterone or vaginal progesterone. The progesterone is all made in the same way, using a semi-synthetic process that converts diosgenin, a steroid found in a type of wild yam, into progesterone.
A transdermal route is not more natural or less natural than an oral route. The natural way is from the ovaries until menopause and then to have no progesterone at all. What matters is does the drug do what it claims and is it safe! Natural is an awful yardstick for hormones, after all, it is the natural estrogen made by the body that gives some women cancer.
There is no credible research showing topical progesterone formulations made by compounding pharmacies do anything, and women who use them and have a uterus and who are also taking estrogen are putting themselves at risk for endometrial cancer. Women who are using these creams who are not using estrogen or who don’t have a uterus are simply buying a placebo. Anyone being told they need salivary hormone testing to follow their progesterone levels is being sold an additional scam.
Providers who recommend topical progesterone and those pharmacies making it are taking advantage of women with menopausal symptoms, or they simply don’t know any better. Neither is a good look.
As for calling topical progesterone a scam? What would you call a product with no proof it helps and the available data suggests it is unsafe for women taking estrogen? Oh yes, and the use of this product is often accompanied by useless tests that require people pay out of pocket?
Yeah, for me that’s a scam.
Wren BG. Transdermal progesterone creams for postmenopausal women: more hype than hope? MJA 2005; 182: 237–239.
National Academies of Sciences, Engineering, and Medicine 2020. The Clinical Utility of Compounded Bioidentical Hormone Therapy: A Review of Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. https://doi.org/10.17226/25791.
'Natural' progesterone creams for postmenopausal women. Drug Ther Bull 2001 Feb;39(2):10-1.
Cooper A, Spencer C, Whitehead MI, et al. Systemic absorption of progesterone from Progest Cream in menopausal women [letter]. Lancet 1998; 351: 1255-1256.
Fugh-Berman A, Bythrow J. Bioidentical Hormones for Menopausal Hormone Therapy: Variation on a Theme. Society of General Internal Medicine 2007;22:1030–1034.
Wren BG. Progesterone creams: do they work? [editorial]. Climacteric 2003; 6: 184-187.
Lewis JG, McGill H, Patton VM, Elder PA. Caution on the use of saliva to monitor absorption of progesterone from transdermal creams in post- menopausal women. Maturitas 2002; 41: 1-6.
Leonetti HB, Longo S, Anasti JM. Transdermal progesterone cream for vasomotor symptoms and postmenopausal bone loss. Obstet Gynecol1999; 94: 225-228.
Burry KA, Patton PE, Hermsmayer K. Percutaneous absorption of progesterone in postmenopausal women treated with transdermal estrogen. Am J Obstet Gynecol 1999; 180: 1504-1511.
Wren BG, McFarland K, Edwards L, et al. Effect of sequential transdermal progesterone cream on endometrium, bleeding pattern and plasma progesterone and salivary progesterone levels in postmenopausal women. Climacteric 2000; 3: 155-160.
Carey BJ, Carey AH, Patel S, et al. A study to evaluate serum and urinary hormone levels following short and long term administration of two regimens of progesterone cream in postmenopausal women. BJOG 2000; 107: 722-726.
Wren BG, Champion SM, Willets K, et al. Transdermal progesterone and its effect on vasomotor symptoms, blood lipid levels, bone metabolic markers, mood, and quality of life for postmenopausal women. Menopause 2003; 10: 13-18.